Recently, a collaborative research team led by Professor Feng Zhu/Bo Yang from the Center for Transformative Molecular Frontier Sciences at Shanghai Jiao Tong University, together with Professor Lingjun Zheng's team from the School of Agriculture and Biology, Dr. Yingzi Li from the Institute of Chemical Research of Catalonia, and Professor Xing Zhang's team from the School of Food Science and Pharmaceutical Engineering at Nanjing Normal University, has made significant research progress.

The study, titled "Stereoselective C(sp³)-Si/Ge Bond Formation via Nickel-Catalyzed Decarboxylative Couplings," has been published in the prestigious international journal Chem.

Article abstract:

The bigger picture：

Carbohydrates are often modified into glycomimetics by replacing labile functional groups with more stable alternatives, thereby enhancing their biological and physicochemical properties. C-glycosides, in particular, have emerged as potent, metabolically stable alternatives to O-glycosides, holding great promise for therapeutic development. However, the substitution of exocyclic oxygen with group 14 elements such as Si and Ge remains a largely unexplored frontier. To address this gap, we have developed the first highly stereoselective decarboxylative C(sp³)-Si and C(sp³)-Ge cross-coupling reaction of NHPI esters with silylzinc and germylzinc reagents. Featuring a broad substrate scope, high stereoselectivity, and mild conditions, this method provides a robust catalytic approach for synthesizing Si- and Ge-glycosides, as well as chiral Si/Ge-containing building blocks, such as germylated and silylated 1,2-amino alcohols and diols for drug design. Importantly, mechanistic studies and density functional theory (DFT) calculations support a unique Ni(0)/Ni(I)/Ni(II) catalytic cycle, providing a redefined understanding of the mechanism behind Ni-catalyzed couplings between NHPI esters and organometallic reagents. Furthermore, preliminary biological evaluations indicate that the unique Ge- and Si-glycosides exhibit promising biological activities and demonstrate significant potential for further biomedical research. From a broader perspective, this study integrates carbohydrate chemistry, organic synthesis, computational chemistry, and chemical biology, providing important guidance for the design of next-generation carbohydrate-based therapeutics.

Highlights：

•Ni-catalyzed decarboxylative C(sp³)–Si/Ge coupling of redox-active esters

•First catalytic, stereoselective synthesis of Si- and Ge-glycosides

•Ge- and Si-glycosides demonstrated promising bioactivity for the first time

•A novel Ni-catalyzed mechanism for the decarboxylative C(sp³)–Si/Ge coupling

Summary：

Glycomimetics are stable carbohydrate analogs in which labile groups are strategically replaced to enhance functionality while maintaining overall structural integrity. While C-glycosides, as glycomimetics of natural O-glycosides, are well-explored, Si- and Ge-glycosides remain underdeveloped due to inefficient C(sp³)-Si/Ge bond formation. Herein, we report the first example of stereoselective C(sp3)-Si/Ge bond formation via nickel-catalyzed decarboxylative coupling of redox-active esters with silylzinc and germylzinc reagents, marking the first catalytic approach for Si- and Ge-glycosides. This method also enables access to chiral Si- and Ge-1,2-amino alcohols and diols, crucial yet underexplored motifs in pharmaceutical chemistry. Mechanistic studies and density functional theory (DFT) calculations reveal an interesting Ni(0)/Ni(I)/Ni(II) catalytic cycle and an unprecedented NHPI ester activation mode, shaping future catalytic strategies for NHPI ester transformations. Preliminary evaluations reveal promising bioactivities of Ge- and Si-glycosides, suggesting their potential in biomedical research. This work establishes a catalytic platform for the synthesis of chiral silylated and germylated compounds.